| Autor: |
Casanova AG; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.; Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.; Toxicology Area, University of Salamanca, 37007 Salamanca, Spain.; Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León, 42002 Soria, Spain.; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), National Network for Kidney Research REDINREN, RD016/0009/0025, Instituto de Salud Carlos III, 37007 Salamanca, Spain., Harvat M; Intelligent Data Analysis Laboratory (IDAL), Dpt. Enginyeria Electrònica, ETSE-UV, Universitat de València, 46100 Valencia, Spain., Vicente-Vicente L; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.; Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León, 42002 Soria, Spain., Pellicer-Valero ÓJ; Intelligent Data Analysis Laboratory (IDAL), Dpt. Enginyeria Electrònica, ETSE-UV, Universitat de València, 46100 Valencia, Spain., Morales AI; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.; Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.; Toxicology Area, University of Salamanca, 37007 Salamanca, Spain.; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), National Network for Kidney Research REDINREN, RD016/0009/0025, Instituto de Salud Carlos III, 37007 Salamanca, Spain.; Group of Biomedical Research on Critical Care (BioCritic), Valladolid University Hospital, 47003 Valladolid, Spain.; Disease and Theranostic Modelling (DisMOD) Working Group, IBSAL, 37007 Salamanca, Spain., López-Hernández FJ; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.; Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.; Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León, 42002 Soria, Spain.; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), National Network for Kidney Research REDINREN, RD016/0009/0025, Instituto de Salud Carlos III, 37007 Salamanca, Spain.; Group of Biomedical Research on Critical Care (BioCritic), Valladolid University Hospital, 47003 Valladolid, Spain.; Disease and Theranostic Modelling (DisMOD) Working Group, IBSAL, 37007 Salamanca, Spain., Martín-Guerrero JD; Intelligent Data Analysis Laboratory (IDAL), Dpt. Enginyeria Electrònica, ETSE-UV, Universitat de València, 46100 Valencia, Spain. |
| Abstrakt: |
The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular filtration rate decline, and azotemia. These alterations are consequences of a primary tubulopathy causing injury to proximal and distal epithelial cells, and thus tubular dysfunction. Oxidative stress plays a role in cisplatin nephrotoxicity and cytotoxicity, but its relative contribution to overall toxicity remains unknown. We studied the relation between the degree of oxidative reduction (provided by antioxidant treatment) and the extent of nephrotoxicity amelioration (i.e., nephroprotection) by means of a regression analysis of studies in animal models. Our results indicate that a linear relation exists between these two parameters, and that this relation very nearly crosses the value of maximal nephroprotection at maximal antioxidant effect, suggesting that oxidative stress seems to be a pivotal and mandatory mechanism of cisplatin nephrotoxicity, and, hence, an interesting, rationale-based target for clinical use. Our model also serves to identify antioxidants with enhanced effectiveness by comparing their actual nephroprotective power with that predicted by their antioxidant effect. Among those, this study identified nanoceria, erythropoietin, and maltol as highly effective candidates affording more nephroprotection than expected from their antioxidant effect for prospective clinical development. |
